T1D‐weighted ihMT imaging – Part I. Isolation of long‐ and short‐T1D components by T1D‐filtering

Hertanu, Andreea; Soustelle, Lucas; Troter, Arnaud Le; Buron, Julie; Priellec, Julie Le; Carvalho, Victor; Cayre, Myriam; Durbec, Pascale; Varma, Gopal; Alsop, David C.; Girard, Olivier; Duhamel, Guillaume

doi:10.1002/mrm.29139

Cited by 7 publications

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“…Because the ihMT increase with reduced duty cycle can be very large, greater than 3-fold, the use of low duty cycle preparations to achieve higher signal and SNR is becoming increasingly preferred. With high RF saturation power, which is typically the case for low duty cycle experiments, the signal contribution from shorter T 1D molecules can become substantial, 38,44,49,50 opening the possibility to image other molecular structures and tissues than myelin. 51,52 The increased sensitivity to short T 1D s does reduce the specificity of the ihMT signal to myelin, however.…”

Section: Optimizing Acquisition Methodsmentioning

confidence: 99%

“…45 The T 1D -filtering principle relies on the sensitivity of ihMT to T 1D when using frequency-alternated pulses with different switching times, τ switch , for the dual-offset saturation experiment (Figure 4), and has been recently characterized. 44 The lengthening of τ switch efficiently attenuates the signal associated with T 1D values shorter than τ switch (even eliminates their contribution when T 1D << τ switch ), thereby generating an ihMT high-pass T 1D filter with increasing cutoff values (Figure 5A). IhMT high-pass T 1D filters with high cutoff values can selectively image longer T 1D contributors and increase the WM/GM contrast (Figure 5C).…”

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

“…In vivo imaging of long and short T 1D components separately can be achieved with ihMT, when using a strategy based on so‐called T 1D filtering 45 . The T 1D ‐filtering principle relies on the sensitivity of ihMT to T 1D when using frequency‐alternated pulses with different switching times, τ switch , for the dual‐offset saturation experiment (Figure 4), and has been recently characterized 44 . The lengthening of τ switch efficiently attenuates the signal associated with T 1D values shorter than τ switch (even eliminates their contribution when T 1D << τ switch ), thereby generating an ihMT high‐pass T 1D filter with increasing cutoff values (Figure 5A).…”

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

“…T 1D ‐filtering effects achieved in images of the mouse brain by varying τ switch 44 . (A) Simulations of inhomogeneous magnetization transfer ratio (ihMTR) as a function of T 1D for different τ switch values shows the preferential attenuation of shorter T 1D signals with increasing τ switch , effectively creating a high‐pass T 1D filter.…”

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

“…The pulses are shown as rectangular to simplify the figure but are detailed in (B). Pulses may be either single pulses that are cosine modulated for dual frequency saturation, or a composite of several pulses where dual frequency saturation is achieved by frequency alternation.F I G U R E 5 T 1D -filtering effects achieved in images of the mouse brain by varying τ switch 44. (A) Simulations of inhomogeneous magnetization transfer ratio (ihMTR) as a function of T 1D for different τ switch values shows the preferential attenuation of shorter T 1D signals with increasing τ switch , effectively creating a high-pass T 1D filter.…”

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Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

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Off resonance RF irradiation can induce the ordering of proton spins in the dipolar fields of their neighbors, in molecules with restricted mobility. This dipolar order decays with a characteristic relaxation time, T 1D , that is very different from the T1 and T2 relaxation of the nuclear alignment with the main magnetic field. Inhomogeneous Magnetization Transfer (ihMT) imaging is a refinement of Magnetization Transfer (MT) imaging that isolates the MT signal dependence on dipolar order relaxation times within motion constrained molecules. Since T 1D relaxation is a unique contrast mechanism, ihMT may enable improved characterization of tissue. Initial work has stressed the high correlation between ihMT signal and myelin density. Dipolar order relaxation appears to be much longer in membrane lipids than other molecules. Recent work has shown, however, that ihMT acquisitions may also be adjusted to emphasize different ranges of T 1D . These newer approaches may be sensitive to other microstructural components of tissue. Here we review the concepts and history of ihMT and lay out needs for further development to realize its full potential.Inhomogeneous magnetization transfer imaging(1), or ihMT, is a refinement of magnetization transfer that provides different contrast between tissues than MT by isolating dipolar order effects within motion restricted molecules(2) that are weighted by the corresponding dipolar relaxation time, T 1D .Because dipolar order relaxation is slower in myelinated tissues than any other tissue observed, it is highly sensitive to myelin. More broadly, the addition of a new relaxation mechanism for MRI that reflects macromolecular structure and mobility and with clearly different properties from T 1 and T 2 opens the possibility of heightened sensitivity to pathology.Though a growing body of literature describes the properties of ihMT MRI, much work remains to realize its potential for research and clinical studies. After a brief introduction, this review is organized around 6 major directions for further investigation and development: 1. Determining the underlying physics and tissue parameters behind ihMT; 2. Estimating, validating, separating, and interpreting different T 1D components; 3. Optimizing acquisition methods; 4. Optimizing quantification methods; 5.

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Section: Optimizing Acquisition Methodsmentioning

confidence: 99%

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

Section: Estimating Validating Separating and Interpreting Different ...mentioning

confidence: 99%

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confidence: 99%

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Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

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T_1D‐weighted ihMT imaging – Part II. Investigating the long‐ and short‐T_1D components correlation with myelin content. Comparison with R₁ and the macromolecular proton fraction

Hertanu

Soustelle

Buron

et al. 2022

Magnetic Resonance in Med

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To investigate the long-and short-T 1D components correlation with myelin content using inhomogeneous magnetization transfer (ihMT) high-pass and band-pass T 1D -filters and to compare ihMT, R 1 , and the macromolecular proton fraction (MPF) for myelin specific imaging. Methods:The 3D ihMT rapid gradient echo (ihMTRAGE) sequences with increasing switching times (Δt) were used to derive ihMT high-pass T 1D -filters with increasing T 1D cutoff values and an ihMT band-pass T 1D -filter for components in the 100 µs to 1 ms range. 3D spoiled gradient echo quantitative MT (SPGR-qMT) protocols were used to derive R 1 and MPF maps. The specificity of R 1 , MPF, and ihMT T 1D -filters was evaluated by comparison with two histological reference techniques for myelin imaging. Results:The higher contribution of long-T 1D s as compared to the short components as Δt got longer led to an increase in the specificity to myelination. In contrast, focusing on the signal originating from a narrow range of short-T 1D s (< 1 ms) as isolated by the band-pass T 1D -filter led to lower specificity. In addition, the significantly lower r 2 correlation coefficient of the band-pass T 1D -filter suggests that the origin of short-T 1D components is mostly associated with non-myelin protons. Also, the important contribution of short-T 1D s to the estimated MPF, explains its low specificity to myelination as compared to the ihMT high-pass T 1D -filters. Conclusion:Long-T 1D components imaging by means of ihMT high-pass T 1Dfilters is proposed as an MRI biomarker for myelin content. Future studies should | METHODS | Animal experimentsAnimal studies were conducted in agreement with the French guidelines for animal care from the French Department of Agriculture (Animal Rights Division), the directive 2010/63/EU of the European Parliament and of enable the investigation of the sensitivity of ihMT T 1D -filters for demyelinating processes.

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Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

Soustelle

Troalen

Hertanu

et al. 2023

Magnetic Resonance in Med

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To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. Methods:The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T 1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction[MPF], T 2,f , T 2,b , R, and free pool T 1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T 1 . Results: Bland-Altman analyses demonstrated a systematic underestimation of MPF (−2.5% and −1.3%, on average, in white and gray matter, respectively) and overestimation of T 1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored.Reproducibility of the proposed framework is excellent (ΔMPF = −0.03% and ΔT 1 = −19.0 ms). The single-point methodology yielded consistent MPF and T 1 values with respective maximum relative average bias of −0.15% and −3.5 ms found in white matter. Conclusion:The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.

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T_1D‐weighted ihMT imaging – Part I. Isolation of long‐ and short‐T_1D components by T_1D‐filtering

Cited by 7 publications

References 41 publications

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

T_1D‐weighted ihMT imaging – Part II. Investigating the long‐ and short‐T_1D components correlation with myelin content. Comparison with R₁ and the macromolecular proton fraction

Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

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T1D‐weighted ihMT imaging – Part I. Isolation of long‐ and short‐T1D components by T1D‐filtering

Cited by 7 publications

References 41 publications

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

Inhomogeneous magnetization transfer imaging: Concepts and directions for further development

T1D‐weighted ihMT imaging – Part II. Investigating the long‐ and short‐T1D components correlation with myelin content. Comparison with R1 and the macromolecular proton fraction

Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

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T_1D‐weighted ihMT imaging – Part I. Isolation of long‐ and short‐T_1D components by T_1D‐filtering

T_1D‐weighted ihMT imaging – Part II. Investigating the long‐ and short‐T_1D components correlation with myelin content. Comparison with R₁ and the macromolecular proton fraction